The ultimate objective of the proposed research is to elucidate the physical principles underlying the use of ultrasound fore the definitive quantification of acoustic properties of heart muscle needed for optimal diagnosis and assessment of function. In clinical echocardiography, scans are made with the direction of propagation of ultrasound at varying angles relative to the local fiber orientation of the myocardium and throughout the contraction-relaxation cycle. We have demonstrated that the magnitudes of backscatter and attenuation vary substantially with the angle of insonification relative to the arrangement of myofibers in the ventricular walls. Anisotropy is responsible for the drop out of the lateral and septal wall echoes in parasternal short-axis echocardiographic views and is especially pertinent for quantitative tissue characterization which has as its goal assessment of the properties of the tissue itself, as opposed to assessment of dimensions or motion. We propose to continue and extend our systematic investigations of the extent of angular variation of the ultrasonic properties of the heart and their relationship to conventional echocardiography, automatic echocardiographic detection of tissue-blood interfaces, myocardial tissue characterization, and ultimately to ultrasonic assessment of myocardial elastic properties. Research during the current grant period has focused on anisotropic properties averaged over the entire thickness of the ventricular wall. In this competitive renewal proposal, we outline studies designed to delineate the transmural variation of elastic properties that parallel significant transmural variations in the three-dimensional architecture of normal and diseased myocardium by measuring the transmural variations of the anisotropy of backscatter, attenuation, and velocity of myocardium and comparing with appropriate experimental and mathematical models. We further propose strategies for overcoming potential stumbling blocks arising from anisotropy for echocardiographic imaging, automatic detection of cardiac chamber dimensions, and myocardial tissue characterization. The proposed research is designed to lay the groundwork for exploiting the anisotropy of myocardial elastic properties to achieve improved understanding of cardiac mechanical properties (elasticity and compliance) in normal and diseases hearts. Our goal is to provide definitive answers to a series of explicit questions posed in the text of the proposal and thus to provide a basis for improving the diagnostic power of ultrasonics.